Gastric Epithelial Neoplasm of Fundic-Gland Mucosa Lineage: Showed the Same Genetic Lineage and Ki67 May Help in Their Identification

Abstract Introduction/Objective Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare form of gastric tumors that encompasses oxyntic gland adenoma (OGA), gastric adenocarcinoma of the fundic-gland type (GA-FG), and gastric adenocarcinoma of the fundic-gland mucosa type (GA-FGM). There is no consensus on the clinicopathologica and molecular characteristics of GEN-FGMLs, and misdiagnosis is common because of similarities in symptoms. Methods/Case Report The NGS and immunohistochemical staining were performed on 37 cases diagnosed with GEN-FGMLs with a thorough histological evaluation. Gene alternations were analysed and compared across histological subtypes. we used an artificial intelligence approach for the recognition of the Ki67 immunohistochemistry stained. Results (if a Case Study enter NA) The patient’s ages ranged from 42 to 79 years, with a median age of 60. 17 were male and 20 were female. Morphologically, 19 OGAs, 16 GA-FGs, and two GA-FGMs were identified. Histopathological similarities exist between GEN-FGMLs. The tumors demonstrated well-formed glands, expanding with dense growth patterns comprising pale, blue-grey columnar cells with mild nuclear atypia. The normal gastric pit epithelium covered the entire surface of the OGA and GA-FG, but the dysplasia pit epithelium covered the GA-FGM. Compared with OGA, GA-FG and GA-FGM were more prominent in the macroscopic view (p<0.05) and had larger sizes (p<0.0001). Additionally, GA-FG and GA-FGM exhibited higher Ki67 indices than OGA (p<0.0001). The heterogeneity of mutational signatures, somatic mutations, and copy number variations was revealed across histological subtypes. The top five mutational signatures in OGA were ROS1, CTNNA1, GNAS, BRCA2, and ZFHX3. The top five mutational signatures in GA-FG and GA-FGM were GNAS, MLL3, BRAF, MSH3, and EGFR. GNAS were both found in OGA, GA-FG and GA-FGM. Compared with well-differencent gastric adenocarcinoma, The top five mutational signatures in GEN-FGMLs were GNAS, BRAF, ROS1, MLL3, and MSH3. Recurrently mutated key signaling pathways across tumor types in GEN-FGML were Wnt signaling pathways. Conclusion GEN-FGMLs are a group of well-differentiated gastric tumors with favourable biological behaviours. Compared with OGA, GA-FG and GA-FGM have larger sizes and higher Ki67 proliferation indices, indicating that they play a critical role in the identification of GEN-FGML. GEN-FGMLs showed the same genetic lineage, the Wnt signalling pathway plays a role in the development and progression of GEN-FGMLs.